The present invention relates to adjuvant combinations comprising two or more different adjuvants. In particular the invention relates to adjuvant compositions comprising the adjuvants in aqueous media for immunization and vaccines.
The invention also relates to vaccines and immunization combination kits comprising two or more adjuvants and an antigenic substance.
Since the English doctor Edward Jenner in 1796 discovered that the infectious agency causing cowpox in cattle was able to produce immunity against smallpox in human beings without causing serious illness many efforts have been made in order to find other vaccines which can generate immunity against more or less severe diseases in animal and human beings without provoking the unpleasant, serious or fatal symptoms and reactions usually accompanying the ordinary diseases in question.
Thus, for example, tuberculosis in man has for many years been combated by vaccination with attenuated but living strains of Mycobacteriurn bovis (BCG vaccine). However, the efficacy of this procedure does not always provide satisfactory resistance to human tuberculosis in every population.
Therefore, attempts have been made to isolate and use fragments or subfragments of strains of human Mycobacterium tuberculosis instead as immunogenic agent which when injected intradermally or subcutaneously in individuals would cause satisfactory immunity against infections with naturally occurring strains of human Mycobacterium tuberculosis. Thus, non-determined substances from culture filtrates as well as a few isolated molecules such as Ag85 and ESAT-6 of Mycobacterium tuberculosis have been shown to provide some degree of tuberculosis immunity. In the future it would be desirable to have vaccines based on well-defined substances which would always create high immunity against tuberculosis and other diseases.
Unfortunately, many highly purified substances, e.g. purified recombinant proteins, are not very immunogenic and do not generate an effective immune response protective against the real infectious disease. This fact has been recognized since the beginning of this century and it has been tried to counteract the low immunogenicity by combining the substance in question with immunogenic response potentiating agents, so-called adjuvants. A large number of such adjuvants and kind of adjuvants have been suggested but in general without any being ideal in all respects.